Development and optimization of stealth liposomal system for enhanced in vitro cytotoxic effect of quercetin

Abstract

The present study was designed to develop a stealth liposomal drug delivery system for a naturally occurring flavonoid, quercetin. Quercetin is a unique polyphenol with multifarious curative applications, anticancer activity being one of them. However, the poor aqueous solubility of this hydrophobic compound hinders its therapeutic effects. For this purpose, our study aimed to enhance the aqueous solubility and in vitro cytotoxic efficacy of quercetin by its incorporation in stealth liposomal formulation. Quercetin-loaded stealth liposomes were prepared with different molar ratios of egg-PC, cholesterol and DSPE-PEG2000 lipids by the traditional thin film hydration method followed by their physicochemical characterization to determine average particle size, polydispersity index (PDI) and zeta potential. The encapsulation efficiency (EE%), saturation solubility of quercetin and apparent solubility of quercetin-loaded stealth liposomes were determined using HPLC. The stealth liposomes were investigated for their stability and an optimized and stable liposomal formulation containing 5% DSPE-PEG2000 lipid was then further evaluated for its in vitro cytotoxicity in HeLa cells and compared to that of free quercetin. The average particle size, PDI, zeta potential and EE% of the optimized liposomes were found to be 110 nm, 0.169, −3.69 mV and 89%, respectively. Encapsulation of quercetin in the stealth liposomal system significantly increased its solubility by approximately 44-fold. This liposomal formulation was stable up to 21 days in terms of its physicochemical characteristics and EE%. Liposomal encapsulation of quercetin was significantly more capable of reducing cell viability of HeLa cells when compared to free quercetin. Our study suggests that this appropriately designed stealth liposomal system could be a promising carrier for encapsulation of the hydrophobic bioactive, quercetin, and significantly enhanced the aqueous solubility and escalated the cytotoxic efficacy of quercetin in cervical cancer cells.